Molecular packing structure of fibrin fibers resolved by X-ray scattering and molecular modeling

Karin A. Jansen, Artem Zhmurov, Bart E. Vos, Giuseppe Portale, Daniel Hermida-Merino, Rustem I. Litvinov, Valerie Tutwiler, Nicholas A. Kurniawan, Wim Bras, John W. Weisel, Valeri Barsegov (Corresponding author), Gijsje H. Koenderink (Corresponding author)

Research output: Contribution to journalArticleAcademicpeer-review

13 Citations (Scopus)

Abstract

Fibrin is the major extracellular component of blood clots and a proteinaceous hydrogel used as a versatile biomaterial. Fibrin forms branched networks built of laterally associated double-stranded protofibrils. This multiscale hierarchical structure is crucial for the extraordinary mechanical resilience of blood clots, yet the structural basis of clot mechanical properties remains largely unclear due, in part, to the unresolved molecular packing of fibrin fibers. Here the packing structure of fibrin fibers is quantitatively assessed by combining Small Angle X-ray Scattering (SAXS) measurements of fibrin reconstituted under a wide range of conditions with computational molecular modeling of fibrin protofibrils. The number, positions, and intensities of the Bragg peaks observed in the SAXS experiments were reproduced computationally based on the all-atom molecular structure of reconstructed fibrin protofibrils. Specifically, the model correctly predicts the intensities of the reflections of the 22.5 nm axial repeat, corresponding to the half-staggered longitudinal arrangement of fibrin molecules. In addition, the SAXS measurements showed that protofibrils within fibrin fibers have a partially ordered lateral arrangement with a characteristic transverse repeat distance of 13 nm, irrespective of the fiber thickness. These findings provide fundamental insights into the molecular structure of fibrin clots that underlies their biological and physical properties.

Original languageEnglish
Pages (from-to)8272-8283
Number of pages12
JournalSoft Matter
Volume16
Issue number35
DOIs
Publication statusPublished - 21 Sept 2020

Funding

We thank Baldomero Alonso Latorre (AMOLF) for help with SAXS data analysis, and Federica Burla (AMOLF) and Fabio Ferri (Universitàdell’Insubria) for help with analysis of the turbidimetry data. This work was part of the research program of the Foundation for Fundamental Research on Matter (FOM), which is financially supported by the Netherlands Organization for Scientific Research (NWO). We gratefully acknowledge access to the DUBBLE BM26B beamline at the ESRF made possible by NWO. WB’s contribution is based upon work supported by Oak Ridge National Laboratory, managed by UT-Battelle, LLC, for the U.S. Department of Energy. NK was supported by a Marie Curie IIF fellowship and a grant from the European Research Council (851960). This work was further supported by the American Heart Association grants 15GRNT23150000 and 13GRNT16960013, NIH grants HL135254 and UO1-HL116330, the University of Pennsylvania Perelman School of Medicine Bridge Funding, the NSF grants DMR 1505662 and DMR 1505316, and the Program for Competitive Growth at Kazan Federal University.

FundersFunder number
Marie Skłodowska‐Curie
National Science FoundationDMR 1505662, DMR 1505316
National Institutes of HealthHL135254, UO1-HL116330
U.S. Department of Energy
American Heart Association13GRNT16960013, 15GRNT23150000
Oak Ridge National Laboratory
Perelman School of Medicine, University of Pennsylvania
European Research Council851960
Stichting voor Fundamenteel Onderzoek der Materie
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
Kazan Federal University

    Fingerprint

    Dive into the research topics of 'Molecular packing structure of fibrin fibers resolved by X-ray scattering and molecular modeling'. Together they form a unique fingerprint.

    Cite this